Lung cancer mutation testing: a clinical retesting study of agreement between a real-time PCR and a mass spectrometry test.

To investigate the clinical validity and utility of tests for detecting Epidermal Growth Factor Receptor (EGFR) gene mutations in non-squamous non-small cell lung cancer patients, tumour DNA extracts from 532 patients previously tested by the cobas EGFR Mutation Test (RT-PCR test) were retested by the Sequenom/Agena Biosciences MassArray OncoFocus mass spectrometry test (MS test). Valid results from both tests were available from 470 patients (88%) for agreement analysis. Survival data were obtained for 513 patients (96%) and 77 patients (14%) were treated with EGFR tyrosine kinase inhibitors (TKIs). Agreement analysis revealed moderately high positive (79.8%), negative (96.9%) and overall percentage agreement (93.2%) for the detection of EGFR mutations. However, EGFR mutations were detected by one test and not by the other test in 32 patients (7%). Retesting of discordant samples revealed false-positive and false-negative results generated by both tests. Despite this, treatment and survival outcomes correlated with the results of the RT-PCR and MS tests. In conclusion, this study provides evidence of the clinical validity and utility of the RT-PCR and MS tests for detection of EGFR mutations that predict prognosis and benefit from EGFR-TKI treatment. However, their false-positive and false-negative test results may have important clinical consequences.

Plasma levels of polychlorinated biphenyls and risk of cutaneous malignant melanoma: a preliminary study.

A number of epidemiologic studies have suggested that exposure to polychlorinated biphenyls (PCB) and other organochlorine compounds (OCC) increase risk of cutaneous malignant melanoma (CMM). However, these studies have generally had no biologic measure of OCC exposure, and have been unable to control for sun exposure, the major known environmental risk factor for this disease. This preliminary study examined the relationship between OCC residues in plasma and risk of CMM adjusting for sun sensitivity and sun exposure. A case-control study of 80 CMM patients and 310 control subjects was conducted. Lifetime sun exposure information, along with data on pigmentation variables and sun sensitivity data was collected, along with a blood sample. Cases and controls were assayed for plasma levels of 14 PCB congeners and 11 organochlorine pesticide residues using gas chromatography. Strong associations were seen between risk of CMM and plasma levels of non-dioxin-like PCBs (Adjusted OR = 7.02; 95% CI: 2.30-21.43 for highest quartile) and several PCB congeners, organochlorine pesticides or metabolites. These associations persisted after control for sun sensitivity and sun exposure. Results from this investigation require independent confirmation in larger studies. However, they suggest that environmental factors other than UV radiation may play a role in genesis of CMM, and indicate that it may be productive to search for further agents which might increase risk.

Clinical pathways to diagnose melanoma: a population-based study.

To better understand the clinical diagnostic process for invasive melanoma in Queensland. Descriptive population-based study of Queensland residents (n=3772) aged 20-75 years diagnosed with invasive melanoma between January 2000 and December 2003. Information was obtained via telephone interview combined with pathology data from the Queensland Cancer Registry. About 85% of melanoma patients diagnosed in Queensland saw a general practitioner at least once during the process, most of these for the initial consultation. Almost one-fifth of patients (18.1%) saw a skin clinic doctor sometime through the diagnosis pathway; this proportion increased significantly over the study period (P<0.001). The most common pathway for diagnosing melanoma was an initial consultation by a general practitioner followed by referral to a surgeon for a definitive diagnosis. People living in southeast Queensland were more likely to see a dermatologist compared with those living in more rural or remote areas (14.7 versus 6.8%), more likely to see a skin clinic doctor (21.8 versus 7.2%), or a surgeon (54.9 versus 49.3%) at least once during the diagnostic process, and less likely to see a general practitioner (76.8 versus 90.2%). This descriptive study has demonstrated the complexity and diversity of clinical diagnostic pathways for melanoma in Queensland, highlighting the important role of general practitioners and the emerging role of primary care skin clinics. Although this system has resulted in a very favourable thickness distribution for diagnosed melanomas, access issues for people living in rural and remote areas of Queensland need to be addressed.

Incidence rates and risk factors of benign breast neoplasms.

A case-control study of benign breast disease was conducted in Greater Boston in 1968-1969. Cases were nearly all women living in the reference population who were initially diagnosed as having fibrocystic disease, fibroadenoma or a "mixed" lesion during the study period. Controls were a random sample of the entire reference population. A mail questionnaire was completed for 678 cases and for 1807 controls. For fibrocystic disease the age-standardized incidence rate was 89.4 per 100,000 woman-years; for fibroadenoma it was 32.8. Fibrocystic disease rises in incidence to age 45 and then declines sharply. The incidence rate of fibroadenoma peaks during the 20's, while that of mixed tumors has a mode at 30 to 34. Among young women, the highest rates occur in married nulliparae, but this is not so at higher ages. Neither for fibroadenoma nor fibrocystic disease was there a consistent relationship of risk with parity or with age at first birth. Fibrocystic disease risk was strongly and directly related to age at natural menopause, directly but not strongly related to an index of socioeconomic status, and was increased among women who gave a history of arthritis. Both fibrocystic disease and fibroadenoma were much less frequent in more obese women. Neither fibrocystic disease nor fibroadenoma has an epidemiologic pattern which corresponds closely to that of breast cancer. Therefore, it seems reasonable to suggest that the apparent increased risk of breast cancer among women with benign breast disease is concentrated within a subset of these women.